1-209763382-A-G

Variant names:

• chr1-209763382-A-G
• NM_025228.4:c.596A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025228.4(TRAF3IP3):​c.596A>G​(p.Asp199Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAF3IP3 NM_025228.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20
• Publications: 0 publications found

Genes affected

TRAF3IP3 (HGNC:30766): (TRAF3 interacting protein 3) The gene encodes a protein that mediates cell growth by modulating the c-Jun N-terminal kinase signal transduction pathway. The encoded protein may also interact with a large multi-protein assembly containing the phosphatase 2A catalytic subunit. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18404323).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025228.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP3	NM_025228.4	MANE Select	c.596A>G	p.Asp199Gly	missense	Exon 7 of 17	NP_079504.2	Q9Y228-1
	TRAF3IP3	NM_001320143.2		c.596A>G	p.Asp199Gly	missense	Exon 7 of 17	NP_001307072.1	Q9Y228-1
	TRAF3IP3	NM_001320144.2		c.536A>G	p.Asp179Gly	missense	Exon 7 of 17	NP_001307073.1	Q9Y228-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP3	ENST00000367025.8	TSL:1 MANE Select	c.596A>G	p.Asp199Gly	missense	Exon 7 of 17	ENSP00000355992.3	Q9Y228-1
	TRAF3IP3	ENST00000367026.7	TSL:1	c.536A>G	p.Asp179Gly	missense	Exon 7 of 17	ENSP00000355993.3	Q9Y228-2
	TRAF3IP3	ENST00000478359.5	TSL:1	n.596A>G		non_coding_transcript_exon	Exon 7 of 13	ENSP00000417665.1	Q9Y228-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PhyloP100		3.2
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.043
Sift	Benign	0.12	T
Sift4G	Benign	0.69	T
Polyphen		0.0060	B
Vest4		0.19
MutPred		0.23		Loss of stability (P = 0.0959)
MVP		0.42
MPC		0.20
ClinPred		0.50	T
GERP RS		4.5
Varity_R		0.11
gMVP		0.27
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr1-209936727;